Lanthanide elements and actinide elements have a number of industrial and medicinal uses. For purposes of interpreting this document and the claims that follow, the term "lanthanide element" is defined to encompass the elements La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu, and the term "actinide element" is defined to encompass the elements Ac, Th, Pa, U, Np, Pu, Am, Cm, Bk, Cf, Es, Fm, Md, No, Lr, Rf, and Ha.
The above-listed lanthanide and actinide elements can be used, for example, as imaging agents. For instance, the elements Tb and Eu are characterized by fluorescence and luminescence, and can be used as probes in biological systems. Yb also has spectroscopic characteristics that enable it to be a useful probe in biological systems.
A difficulty in utilizing the lanthanide or actinide elements as probes in biological systems is in localizing the elements to specific areas of a biological system which are to be probed. Accordingly, it would be desirable to bind lanthanide or actinide elements to a transport compound which would specifically transport the elements to a localized region of a biological system.
Another use of lanthanide and actinide ions is as cell toxicity agents. For example, .sup.225 Ac is a radioactive element which decays successively to Bi-209 by emission of four alpha particles. Alpha particles are lethal to cells when they traverse cell nuclei in close proximity to the radioactive source. Accordingly, .sup.225 Ac has utility for cancer treatment. A difficulty in utilizing .sup.225 Ac for cancer treatment is to localize the .sup.225 Ac within close proximity to cancer cells. Accordingly, it would be desirable to develop a transport compound that would specifically transport .sup.225 Ac to cancer cells in a biological system.
In recent years there has been an increased interest in the development of monoclonal antibodies that specifically target cancer cells and tumors. It is thought that such antibodies can be labeled with radionuclides and utilized to transport the radionuclides to cancer cells and tumors for utilization in radioimmunodiagnosis and radioimmunotherapy of cancer. The success of such approaches depends on development of bifunctional complexing agents that can bind a radionuclide strongly and selectively, and that can be further linked to antibodies. Accordingly, it would be desirable to develop such bifunctional complexing agents.
A recently discovered class of compounds known as calixarenes, or "molecular baskets", show potential for being able to tightly and selectively bind a number of different elements. Calixarenes are cyclic oligomers made up of phenolic units meta-linked by methylene bridges and possessing bowl-shaped cavities. To specify a size of a calixarene, one intercalates between brackets a number that represents the number of phenolic units constituting calixarene. Four formulaic representations of a prior art calix[4]arene are illustrated in FIG. 1 as "A", "B", "C" and "D". Each formulaic representation has several R-groups. The R-groups represent alkyl groups, such as t-butyl groups. In the formulaic representation labeled "C", it shown that a calixarene can be thought of as a compound containing an upper rim 10 and a lower rim 12. A plurality of hydroxyl groups of the calixarene are attached to lower rim 12.
Calixarenes are relatively easy to synthesize. For example, many calixarenes can be synthesized by a one-pot base-induced condensation of p-substituted phenol and formaldehyde.